A sedentary lifestyle, obesity, and a Westernized diet have been implicated in the aetiology of both colorectal cancer and non-insulin dependent diabetes mellitus, leading to the hypothesis that hyperinsulinaemia may promote colorectal cancer. We prospectively examined the association between colorectal cancer risk and factors related to insulin resistance and hyperinsulinaemia, including BMI, physical activity, diabetes mellitus, and blood glucose, in a cohort of 75 219 Norwegian men and women. Information on incident cases of colorectal cancer was made available from the Norwegian Cancer Registry. Reported P values are two-sided. During 12 years of follow up, 730 cases of colorectal cancer were registered. In men, but not in women, we found a negative association with leisure-time physical activity (P for trend = 0.002), with an age-adjusted RR for the highest versus the lowest category of activity of 0.54 (95% CI = 0.37-0.79). Women, but not men, with a history of diabetes were at increased risk of colorectal cancer (age-adjusted RR = 1.55; 95% CI = 1.04-2.31), as were women with non-fasting blood glucose > or = 8.0 mmol l(-1)(age-adjusted RR = 1.98; 95% CI = 1.31-2.98) compared with glucose <8.0 mmol l(-1). Overall, we found no association between BMI and risk of colorectal cancer. Additional adjustment including each of the main variables, marital status, and educational attainment did not materially change the results. We conclude that the inverse association between leisure-time physical activity and colorectal cancer in men, and the positive association between diabetes, blood glucose, and colorectal cancer in women, at least in part, support the hypothesis that insulin may act as a tumour promoter in colorectal carcinogenesis.